We demonstrate that local, anti-FAP NIR-PIT can successfully and selectively deplete FAP+ immunosuppressive CAFs and myeloid cells in the TME, which results in activation of CD8 T and NK cells, production of IFN-γ, and suppression of tumor growth in both the subcutaneous LL/2 and spontaneous MMTV-PyVT tumors. The gene discussed is FAP; the disease is neoplasm.